This application requests partial support for the scientific program of a combined Keystone Symposium in Copper Mountain, CO, in 1992. These symposia provide a forum for the exchange of scientific information on fundamental and applied aspects of human and medical genetics, and promote personal contacts among the international community of scholars in this rapidly-advancing field. This meeting comes at a time when important advances and powerful analytical techniques in elucidating the basic molecular genetics of eukaryotic organisms are being directed at the clinical practice of human genetics: recombinant DNA, DNA- and chromosome-mediated gene transfer, flow cytometry, polymerase chain reaction, homologous recombination, and transgenic animals. This combined symposium will bring together recognized international experts in two major areas: (1) the newest technologies for identifying and cloning important human disease genes; (2) gene transfer strategies for the eventual facilitation of gene therapy. Gene isolation allows improved diagnostic capabilities, but raises questions concerning the biological function of gene products. The use of transgenic animals as tools to dissect gene function, and the ability to exchange or replace genetic information by homologous recombination will be presented. Improved technologies are needed for positional cloning, cloning by evolutionary homology, and delineating the functions of genes isolated by these techniques; the program will include strategies for exploitation of these procedures. A wide variety of vector systems applied to gene transfer will also be evaluated for expression and function in development in cells, organs, and whole animals. Specific human genetic diseases, especially those most likely to be candidates for gene therapy in the near future, will be discussed in detail, as will the knowledge gained from experience with contiguous gene deletion syndromes and genomic imprinting. This symposium combines two meetings, "The Molecular Biology of Human Genetic Disease" and "Gene Transfer, Replacement, and Augmentation". The projected program includes separate sessions dealing with the main foci described above, as well as joint sessions of common interest to the combined audience of participants.